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June 30, 2005

Genetic On-off Switches Pinpointed in Human Genome

by Sam Savage

In another step to decipher information in the human genome, scientists have discovered the location and sequence of over 10,000 DNA regions that function as genetic on-off switches, or "promoters" in human fibroblasts.

Fibroblasts are relatively generic, easily maintained, human cells that form connective tissues throughout the body. By knowing the specific sequences of DNA that control the nearly 8,000 active genes in fibroblasts, scientists can tease apart the biochemical regulation system these cells use to turn genes on and off during normal growth.

The so-called "promoter map" will not only provide new insight into how genes are controlled in fibroblasts, but will also serve as a framework for analysis of genetic control in other human cell types, tissues and perhaps organs.

The project, detailed in a June 29 electronic edition of the journal, Nature, is a collaboration headed by Bing Ren at University of California, San Diego, working with scientists at University of California, Los Angeles (UCLA) and the company Nimblegen, Inc., in Madison, Wisc.

Understanding the on-off control mechanisms will further understanding of how a cell is programmed to perform specialized functions. Nearly all cells in the human body have the same genetic information. But they don't all express it at the same time.

Cells in the heart, for example, express different information than do cells of the liver or brain. Controlled gene activity at certain times determines what function the cell will have in the body.

To accomplish the genome-wide promoter survey, Bing Ren and his co-worker, Tae Hoon Kim, conceived and designed a novel experimental procedure based on cutting-edge microarray technology. UCLA's Yingnian Wu and Ming Zheng developed sophisticated computer algorithms to process the massive amount of data collected from the experiments.

The researchers report that multiple promoters often control a single gene in parallel, adding another layer to an already complex genetic regulation mechanism. They also discovered promoters in front of DNA sequences not previously recognized as genes. The significance of that finding will be determined in future studies.